MOLECULAR AND CLINICAL ONCOLOGY 9: 231-237, 2018

Coexistence of , , endometrial and myometrial lesions in resected uterine specimens

SEZA TETİKKURT1, ELİF ÇELİK1, HAZAL TAŞ1, TUĞÇE CAY1, SELMAN IŞIK2 and ABDULLAH TANER USTA3

Departments of 1Pathology, and 2Obstetrics and Gynecology, Bağcılar Training and Research Hospital, University of Health Sciences, Istanbul 34200; 3Department of Obstetrics and Gynecology, Acıbadem University, Istanbul 34718, Turkey

Received April 5, 2018; Accepted June 12, 2018

DOI: 10.3892/mco.2018.1660

Abstract. The present study was conducted to identify adenomyosis may be an important factor for the determination endometrial and myometrial lesions coexisting with adenomy- of prognosis. osis, and to evaluate the clinicopathological characteristics of endometrial associated with adenomyosis. Introduction A retrospective analysis of the resected uterine specimens of 319 patients with adenomyosis admitted between January 1, Adenomyosis is defined as the benign infiltration of the endo- 2014 and August 1, 2017 was performed. The endometrial and metrium into the , leading to a diffusely enlarged myometrial lesions coexisting with adenomyosis were evalu- that microscopically exhibits ectopic, non‑neoplastic ated. The clinicopathological prognostic factors, including endometrial glands and stroma, surrounded by hypertro- tumor grade, myometrial invasion, lymphovascular space phic and hyperplastic myometrium (1). During periods of involvement, lymph node invasion, pathological stage and regeneration, healing and re‑epithelisation, the recurrence, were analysed. For data analysis, the Chi‑squared may invade a predisposed myometrium or a traumatised test was used and a P‑value of <0.05 was considered to indi- endometrial‑myometrial interface. Hormonal, genetic and cate statistically significant differences. The mean age of the immunological factors may be implicated in this sequence of patients was 52.1 years. A total of 32 patients had endome- events (2). trial carcinoma associated with adenomyosis. In addition Until recently, adenomyosis was retrospectively diagnosed to endometrioid adenocarcinoma of different grades, rare upon histological examination of uterine specimens. The clear cell carcinoma cases were also observed. Two cases of epidemiological nature of adenomyosis was well‑correlated malignant mesenchymal tumors (one low‑grade endometrial with women who had undergone for abnormal stromal sarcoma and one leiomyosarcoma) were also diag- uterine bleeding. Among hysterectomy specimens, the nosed. Therefore, patients presenting with abnormal uterine reported incidence of adenomyosis in the literature varies, bleeding should undergo thorough evaluation for the presence ranging from an incidence as high as 61.5% to as low as of adenomyosis and/or leiomyoma(s). Although the cases of 8.8% (1,3‑9). The histological diagnosis of adenomyosis endometrial adenocarcinoma associated with adenomyosis primarily depends on the detection of endometrial glands and generally had a good prognostic outcome, there were also stroma within the myometrium, located at a distance from the rare cases of patients with agressive tumor morphology. The endometrio‑myometrial junction (10). The minimum distance inflammatory and tissue response arising around the foci of mandatory for diagnosis is controversial, with a range of 2 mm adenomyosis generate a preventive mechanism against the to >4 mm, or 1‑2 low‑power fields (11). This wide discrepancy invasion of adenocarcinomas coexisting with adenomyosis. in prevalence is partially due to the difference in histological This response is likely the primary mechanism underlying the criteria used for diagnosis, and partially due to the difference good clinical course of these tumors. Therefore, the presence of in frequency of comorbidities that necessitated hysterectomy in different populations (3). Coexisting pathologies, such as leiomyoma, , endometrial , and endometrial carcinoma, are frequently asso- ciated with adenomyosis (12). The high incidence of these pathological lesions associated with adenomyosis suggest the Correspondence to: Dr Seza Tetikkurt, Department of Pathology, presence of a common underlying disorder, such as hyperes- Bağcılar Training and Research Hospital, University of Health trogenism (1,13). Sciences, Dr. Sadık Ahmet Caddesi, Merkez Mahallesi, Bağcılar, Istanbul 34200, Turkey The presence of adenomyosis in determining the prognosis E‑mail: [email protected] of endometrial remains controversial. The aim of the present study was to evaluate the histopathological pattern Key words: adenomyosis, leiomyoma, endometrial adenocarcinoma, of the hysterectomy specimens obtained from patients with endometrioid adenocarcinoma, prognosis adenomyosis presenting with abnormal uterine bleeding, endo- metrial carcinoma, and other causes. Another objective was to 232 TETİKKURT et al: COEXİSTENCE OF ADENOMYOSİS, ADENOCARCİNOMA, ENDOMETRİAL assess the clinical and pathological prognostic characteristics metrium and myometrium associated with adenomyosis are of patients with adenocarcinoma. summarized in Table I. The distribution of endometrial and myometrial characteristics with associated pathological find- Patients and methods ings according to different age groups is presented in Table II.

Ethics. This is a retrospective observational cohort study. Types of endometrial lesions. Endometrial polyps were Prospective ethical approval (2017/#604 Project) was obtained found in 71 cases, while hyperplasia was present in 9 cases. from the Human Research Ethics Commitee at the Bagcılar Simultaneous presence of endometrial polyp and hyperplasia Training and Research Hospital. The research was conducted was identified in 6 patients. Disordered proliferative endome- in accordance with the ethical standarts laid down in the trium was observed in 11 patients. Disordered proliferative 1964 Helsinki Declaration and its later amendments. endometrium, endometrial polyps, and hyperplasia due to hyperestrogenemia were significantly more common among Patient information. A total of 319 patients who had under- patients aged 41‑55 years old (P=0.042). Carcinoma was more gone radical abdominal, vaginal or laparoscopic hysterectomy, frequent among patients in the advanced age (>55 years old) with or without salpingo‑oophorectomy, and with histopatho- group (>55 years; P=0.0001). Similar to adenomyosis, leio- logically diagnosed adenomyosis or with other pathological myoma was significantly more prevalent in the 41‑55 years age conditions, who were diagnosed between January 1, 2014 and group (P=0.003). The two malignant mesenchymal tumors August 1, 2017 at the Bağcılar Training and Research Hospital identified were a low‑grade endometrial stromal sarcoma and Pathology Laboratory (Istanbul, Turkey), were evaluated in a leiomyosarcoma. Endometrial adenocarcinoma was diag- this study. nosed in 32 patients. The age distribution and pathological Epidemiological, clinical and pathological data were prognostic parameters of patients with endometrial carcinoma retrieved from patient records. For all patients, demographic associated with adenomyosis are presented in Table III. data including age, presenting symptoms and previous use No endometrial carcinoma arising from foci of adeno- of , were documented. The criteria for the diag- myosis was observed among our patients. However, infiltration nosis of adenomyosis included the presence of endometrial of adenomyotic foci by adenocarcinoma was diagnosed in glands and stroma at a distance of more than one‑half of a 3 cases. Atypical endometrial hyperplasia was identified in low‑power field (~2.5 mm) in the myometrium when measured 2 cases, and hyperplasia without atypia in 1 case. In the only from the lower border of the endometrium (4,5,14). The age case of dedifferentiated endometrioid carcinoma, the tumor distribution of our cases was 30‑40, 41‑55 and >55 years. was polypoid and there was no myometrial invasion. Age‑dependent physiological changes (endometrial atrophy, basal endometrium, cycle‑dependent changes), gestagenic Postoperative treatment and follow‑up. Following surgery, the effect alterations, hyperestrogenemic conditions (endometrial patients received chemotherapy and radiotherapy according to polyp, disordered proliferative endometrium, hyperplasia) the final pathological stage, if indicated. The mean follow‑up and carcinomas were evaluated as four different groups. The period of the 31 patients was 26.4 months (range, 8‑44 months). myometrial characteristics were classified as normal, leio- At 38 months, 1 patient was diagnosed with pelvic tumor myoma, carcinoma infiltration, hyperplasia without atypia, recurrence. Endometrial carcinoma patient no. 6 succumbed atypical hyperplasia in an adenomyotic focus and malignant to mortality due to the surgical complications on the 10th mesenchymal lesions. In adenocarcinoma cases, tumor grade postoperative day. [according to the International Federation of Gynecology and Obstetrics grading system (15)] depth of myometrial invasion, Preoperative findings. The preoperative clinical findings lymphovascular space involvement, lymph node involvement included: abnormal uterine bleeding in 75 patients (23%), and tumor stage were determined according to the 8th edition leiomyoma in 62 (19%), abnormal uterine bleeding due to of pTNM staging system (16). leiomyoma in 37 (11%), in 28 (8%), in 25 (7.8%), endometrial carcinoma in 24 (7.5%), Statistical analysis. The statistical analysis was performed cervical lesions (CIN etc.) in 13 (4%), atypical endometrial using the Number Cruncher Statistical System 2007 statis- hyperplasia in 9 (2.8%), simple endometrial hyperplasia in tical software program. Continous variables were assessed 9 (2.8%), adenomyosis in 5 (1.5%), pelvic mass in 5 (1.5%), for normality and summarized using mean as appropriate. endometrial polyp in 5 (1.5%), leiomyoma and adnexal mass Differences between categorical variables were assessed using in 5 (1.5%), tamoxifen treatment for breast carcinoma in the Chi‑squared test, frequency, and percentage distribution of 5 (1.5%), non‑uterine malignancies in 4 (1.2%), adnexal mass data in addition to definitive statistical methods. P<0.05 was with abnormal uterine bleeding in 3, and leiomyoma and endo- considered to indicate a statistically significant difference. metrial polyp in 2 patients. Less common findings in three patients included simple endometrial hyperplasia and endo- Results metriosis, endometriosis, and cervical stenosis with abnormal uterine bleeding. Patient characteristics. The mean age ± standard deviation of the patients who underwent hysterectomy was 52.11±14.8 years Discussion (range, 28‑88 years). Most of the patients (71.79%) with adenomyosis were aged between 41 and 55 years of age. The Adenomyosis is a common incidental finding that is frequently patient age and histopathological characteristics of the endo- detected after hysterectomy. The recent advances in diagnostic MOLECULAR AND CLINICAL ONCOLOGY 9: 231-237, 2018 233

Table I. Distribution of age and pathological findings among with that of other histological types of EC (25). Adenomyosis patients. has been documented to coexist with EEC in 16‑34% of the hysterectomy specimens resected for the treatment of EEC. In Variables n % the present study, the incidence of adenocarcinoma associated with adenomyosis was 10%, which was lower compared with that Age, years reported in previous studies, and was more frequent in women 30‑40 9 2.82 aged >55 years (26‑30). Endometrial polyps, hyperplasia with 41‑55 229 71.79 or without atypia, and adenocarcinoma are also more frequent >55 81 25.39 among women with adenomyosis. Bergholt et al reported a Endometrial findings significant association between adenomyosis and endometrial Endometrial atrophy, basal endometrium, 179 56.11 hyperplasia (3). An association between high concentrations of cycle‑dependent changes and adenomyosis, and elevated estrogen concentration in the menstrual blood of women with adenomyosis, were also Changes of gestagenic effect 11 3.45 previously reported (21,31). In addition, relatively high estrogen Endometrial polyp, disordered proliferative 97 30.41 biosynthesis due to aromatase activity in human adenomyotic endometrium, endometrial hyperplasia tissue has been described, and the high level of estrogen was Endometrial carcinoma 32 10.03 suggested to contribute to the growth of adenomyosis (32,33). In Myometrial findings the present study, lesions such as polyps, disordered prolifera- Normal myometrium 133 41.69 tive endometrium, or hyperplasia, were found to be associated Leiomyoma 178 55.80 with hyperestrogenemia in approximately one‑third of the Carcinoma infiltration and hyperplasia 6 1.88 patients. Adenomyosis coexisted with polyps, hyperplasia, and in adenomyotic foci adenocarcinoma in 129 cases (40.4% of all the patients). This Malignant mesenchymal lesions 2 0.63 high ratio indicates the significance of hyperestrogenemia in the development of adenomyosis. n, patient number. The role of adenomyosis presence in estimating the prog- nosis of EEC is a subject of debate, despite the fact that the majority of the studies have reported an excellent prognosis for EEC with concomitant adenomyosis due to the lower histo- imaging techniques, such as transvaginal sonography, logical grade and superficial myometrial invasion detected in hysterosalpingography and magnetic resonance imaging such cases (26,27,29). Gizzo et al suggested an inverse correla- have improved the accuracy of the identification of adeno- tion between myometrial invasion and adenomyosis that may myosis (17). The prevalence of adenomyosis in hysterectomy be due to a possible altered mechanism between the patients was found to be 16.5% by Siddegowda et al (18) and adenomyosis foci and the cancer cells, or by a lower cancer was most commonly observed between 31 and 50 years of aggressiveness associated with the coexistence of adeno- age. In our study, the youngest patient with adenomyosis was myosis (34). However, there is controversy regarding the role of 28 while the oldest was 88 years old. The majority (71.8%) of adenomyosis in EEC, in terms of whether it actively promotes adenomyosis patients belonged to the 41‑55 years age group, or interferes with myometrial invasion of EC (30). Ismiil et al which was consistent with other studies (12,19). reported that the presence of adenomyosis in EEC cases may Stronger and more diffuse cytoplasmic E2 receptor be associated with a poorer prognosis, as it is recognized as a immunoreactivity was detected in the endometrium and precursor of EEC, and as an enabling factor allowing malig- myometrium of adenomyotic foci compared with the normal nant cells to invade the myometrium by increasing the contact endometrium. Higher concentration of E2, but not P4, were area (35). In the present study, there were three cases of grade 3 also detected in the serum of adenomyotic cows compared adenocarcinomas and one case of dedifferentiated endometrioid with that of healthy cows (20). In another study, high levels carcinoma. The aforementioned adenocarcinomas exhibited a of estrogen were found in the menstrual blood of women high‑to‑intermediate differentiation, while high‑grade tumors with adenomyosis (21). Leyendecker et al suggested that and clear cell carcinomas may occasionally be encountered. endometriosis and adenomyosis arise from the exaggeration These patients had a good clinical prognostic outcome of the basically physiological mechanism of tissue injury and during the follow‑up. Our findings suggest that the inflam- repair, involving local estrogen production (22). Moreover, matory response against tissue injury and the smooth muscle they suggested that the non‑pregnant uterus appear to impose hyperplasia induced by the secreted growth factors may have a significant chronic mechanical strain on the subendometrial restricted the expected invasive potential of adenocarcinomas. stromal cells that may lead to local inflammation and prolif- Similar changes in the microenvironment surrounding the deep eration of the basal endometrium into the uterine wall, with adenomyotic foci are responsible for the known complications of the ensuing development of adenomyotic lesions (22,23). endometriosis (22,23,36‑38). The longest follow‑up duration was Endometrial cancer (EC) is the most common malignant 44 months in our patient group, while longer follow‑up periods of the female reproductive tract in developed coun- may better delineate patient prognosis. Lymphadenectomy was tries (24). The most commonly diagnosed histological subtype not performed in a proportion of the patients due to superficial is the endometrioid EC (EEC), which is characterized by a lower myometrial invasion. Although there was no recurrence in this aggressiveness and a higher long‑term disease‑free survival group of patients, the probability of microinvasion or submicro- following adequate primary and adjuvant treatment compared metastasis cannot be ruled out entirely. 234 TETİKKURT et al: COEXİSTENCE OF ADENOMYOSİS, ADENOCARCİNOMA, ENDOMETRİAL

Table II. Distribution of endometrial and myometrial findings with associated lesions according to age.

Age, years [n (%)] ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ Microscopic findings ofthe resected specimens 30‑40 years 41‑55 years >55 years P‑valuea

Endometrium Endometrial atrophy, basal endometrium, 6 (66.67) 141 (61.57) 32 (39.51) - cycle‑dependent changes Changes of gestagenic effect 0 (0.00) 9 (3.93) 2 (2.47) 0.826 Endometrial polyp, DPE and 2 (22.22) 65 (28.38) 30 (37.04) 0.042 endometrial hyperplasia Endometrial carcinoma 1 (11.11) 14 (6.11) 17 (20.99) 0.0001 Myometrium Normal myometrium 3 (30.00) 82 (35.81) 48 (60.00) - Leiomyoma 6 (60.00) 143 (62.45) 29 (36.25) 0.003 Carcinoma infiltration and hyperplasia‑atypical 1 (10.00) 2 (0.87) 3 (3.75) 0.074 hyperplasia in adenomyotic focus Malignant mesenchymal lesions 0 (0.00) 2 (0.87) 0 (0.00) 0.357 aChi‑squared test. DPE, disordered proliferative endometrium.

Adenocarcinoma may involve foci of adenomyosis (39). specimens of patients with concurrent fibroids. The reported Koshiyama et al reported that the adenocarcinoma ratio incidence of concurrent fibroids is 19‑57% (2,6,7,44‑46). In a was 16% in cases of adenomyosis (40). Adenocarcinomas study by Shrestha et al on 150 patients, 52% had adenomyosis arising from adenomyotic foci were not identified in any of without fibroids, 18% had both adenomyosis and fibroids, and the cases involved in the present study. Kucera et al observed 30% had only fibroids (47). In a large series, adenomyosis was that, in the majority of cases with malignant transformation diagnosed histologically in 8% of the cases, while concomitant of adenomyosis, different stages of atypical or hyperplastic adenomyosis and leiomyomas were diagnosed histologically changes were simultaneously identified. This observation in 20% of the patients. Of the patients with adenomyosis, 70% indicates a similar pathway of carcinogenesis in adenomyosis were premenopausal (48). In the present study, adenomyosis as in estrogen‑responsive endometrial cancer type I (29). In was associated with leiomyoma in 55% of the cases. This addition, adenocarcinoma infiltration in the adenomyotic foci incidence was notably higher compared with that reported was observed in three cases, atypical hyperplasia in two cases, by previous studies, indicating that pathogenetic factors may and hyperplasia without atypia in one case. Our findings point be similar between adenomyosis and leiomyoma, mainly in to the possibility that these lesions may have occured as a patients aged 41‑55 years. primary coincidental neoplasia, rather than the infiltration by Based on clinical reports, tamoxifen appears to be a adenocarcinoma arising from eutopic endometrium. crucial risk factor. Tamoxifen exerts anti‑estrogenic effects For uterine leiomyomas, the factors associated with tumor- on the breast through a complex mechanism. It also exerts igenesis may be subdivided into four categories: Predisposing estrogenic effects on other tissues, including the endometrium. or risk factors, initiators, promoters and effectors. Increased This agent is widely used in the treatment of risk may also be associated with early menarche, nulliparity and chemoprevention in high‑risk pre‑ and postmenopausal and , whereas decreased risk has been associated with women. Tamoxifen has been shown to cause adverse effects increasing parity and smoking. Risk factors for fibroids may at the uterine level, the most serious being endometrial carci- achieve significance through their contribution to either the noma and uterine sarcoma (49). Tamoxifen is an antagonist of initiation or the progression of tumorigenesis. Although their the estrogen receptor in breast tissue. Via its active metabolite, impact often appears to be due to their effects on estrogen hydroxytamoxifen, it acts like an agonist leading to develop- and progesterone, other mechanisms may also be involved. ment or reactivation of adenomyosis (50). Adenomyosis occurs Estrogen and progesterone are promoters of fibroid growth more commonly than is generally realized in women using acting synergistically (41). Several studies have reported that tamoxifen, and may account for the postmenopausal bleeding the mRNA and protein expression levels of estrogen receptor‑α in women treated with this agent for breast cancer (51‑53). and ‑β are higher in leiomyoma compared with those in normal Bleeding occurs more frequently among women with endo- myometrium (42,43). The levels of several growth factors and metrial hyperplasia, endometrial carcinoma, or those who their receptors are increased in fibroids. Growth factors may be use tamoxifen (3). A total of five patients in our study had a the mediators or effectors of sex steroid upregulation, while a history of tamoxifen treatment. The abovementioned data primary dysregulation of one or more growth factors must also and our findings indicate that estrogen plays a key role in the be considered (41). Adenomyosis is common in hysterectomy pathogenesis of adenomyosis. MOLECULAR AND CLINICAL ONCOLOGY 9: 231-237, 2018 235

Table III. Histopathologic parameters for prognosis of adenocarcinoma cases.

Case no. Age, years Tumor grade MI, % LVSI LNI Stage (TNM) Recurrence

1 44 2 <50 + PWL p (T1aNxMx) - 2 50 2 >50 - 0 p (T2N0Mx) ‑ 3 56 1 <50 - PWL p (T1aNxMx) - 4 50 2 <50 - 0 p (T1aN0Mx) - 5 61 2 <50 - 0 p (T1aN0Mx) - 6 71 3 >50 - 0 p (T1bN0Mx) Deceased 7 66 2 <50 - 0 p (T1aN0Mx) - 8 72 2 >50 + 0 p (T1bN0Mx) - 9 48 1 <50 - 0 p (T1aN0Mx) - 10 34 1 - - PWL p (T1aNxMx) - 11 52 2 <50 + 0 p (T1aN0Mx) Pelvic 12 46 2 - - 0 p (T1aN0Mx) - 13 65 Dedifferentiated - - 0 p (T1aN0Mx) - endometrioid Ca 14 68 1 >50 - PWL p (T1bNxMx) - 15 48 1 <50 - PWL p (T1aNxMx) - 16 42 1 <50 - PWL p (T1aNxMx) - 17 62 2 >50 - 1 p (T1bN1aMx) - 18 61 1 - - PWL p (T1aNxMx) - 19 56 3 <50 + PWL p (T1aNxMx) - 20 58 2 >50 + PWL p (T1bNxMx) - 21 66 Clear cell Ca <50 - 0 p (T1aN0Mx) - 22 56 1 <50 - PWL p (T1aNxMx) - 23 57 1 <50 - PWL p (T1aNxMx) - 24 49 2 <50 - PWL p (T1aNxMx) - 25 62 1 <50 - 0 p (T1aN0Mx) - 26 51 1 <50 - PWL p (T1aNxMx) - 27 43 2 <50 - PWL p (T1aNxMx) - 28 51 1 <50 - PWL p (T1aNxMx) - 29 53 Mixed Ca (endometrioid >50 - 1 Yp (T2N1aMx) - + clear cell Ca) 30 57 1 <50 - PWL p (T1aNxMx) - 31 72 2 >50 - PWL p (T1bNxMx) - 32 62 3 <50 + PWL p (T1aNxMx) -

TNM, TNM Classification of Malignant Tumours; MI, myometrial invasion; LVSI, lymphovascular space involvement; LNI, lymph node involvement; PWL, patient without lymph node dissection; Ca, carcinoma.

Although this pathological entity has long been known, were diagnosed as adenomyosis, whereas leiomyoma was reliable epidemiological studies are scarce, since the diagnosis observed in 28.19% of the performed for of adenomyosis was only possible postoperatively in the past. abnormal uterine bleeding (55). Weiss et al concluded that The majority of symptomatic women treated for adenomyosis adenomyosis is mostly an incidental finding and may not are in the fourth or fifth decades of life and multiparous (52). be the source of symptomatology for women undergoing The initial symptoms of adenomyosis are non‑specific and hysterectomy (6). In the present study, the most frequent (23%) may also be observed in a number of other disorders, such preoperative symptom was abnormal uterine bleeding. In as dysfunctional uterine bleeding, leiomyomas and endome- addition, only hysterectomy specimens following surgery for triosis. In a study by Mehla et al, adenomyosis was the most lesions coexisting with adenomyosis were evaluated; therefore, frequent cause of abnormal uterine bleeding. The overall this was not an epidemiological study. incidence of adenomyosis was 46.78%, leiomyoma was found The most crucial factor in the pathogenesis of adeno- in 39.9%, while both coexisted in 13.30% of the cases (54). myosis appears to be hyperestrogenemia. In conclusion, a Isaoğlu et al reported that 30.23% of the hysterectomy cases meticulous evaluation and screening should be performed for 236 TETİKKURT et al: COEXİSTENCE OF ADENOMYOSİS, ADENOCARCİNOMA, ENDOMETRİAL adenomyosis, particularly in patients in the fourth and fifth 3. Bergholt T, Eriksen L, Berendt N, Jacobsen M and Hertz JB: Prevalence and risk factors of adenomyosis at hysterectomy. decades of life, in addition to leiomyoma. Radiological assess- Hum Reprod 16: 2418‑2421, 2001. ment is initially recommended for such patients to detect the 4. 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